Evidence map›Paper›PMID 40950130›Full record

ArticlebioRxiv : the preprint server for biology2025

Morphogen-guided neocortical organoids recapitulate regional areal identity and model neurodevelopmental disorder pathology.

Yuan-Chen Tsai, Hajime Ozaki, Xinyi Wang, Axel A Almet, Isabel Fleming, Kaori Shiraiwa, Matthew Jung Min Noh, Caihao Nie, Sunnyana Trejo, Bret Kiyoshi Sugita and 7 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Yuan-Chen TsaiDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0001-5250-0646
Hajime OzakiDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Xinyi WangDepartment of Mathematics, School of Physical Sciences, University of California, Irvine, Irvine, CA, USA.
Axel A AlmetDepartment of Mathematics, School of Physical Sciences, University of California, Irvine, Irvine, CA, USA.
Isabel FlemingDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Kaori ShiraiwaDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Matthew Jung Min NohDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Caihao NieDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Sunnyana TrejoDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Bret Kiyoshi SugitaDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Jiya DalalDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Ruben Alberto GonzalezDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Briana De JesusDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Gregory Li-Min ChenDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.
Michael J GandalDepartment of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Qing NieDepartment of Mathematics, School of Physical Sciences, University of California, Irvine, Irvine, CA, USA.
Momoko WatanabeDepartment of Anatomy and Neurobiology, School of Medicine, University of California, Irvine, Irvine, CA, USA.ORCID 0000-0001-5014-2849

Funding

Isoform-level probabilistic transcriptome-wide association to undercover neurogenetic mechanisms underlying complex psychiatric traitsR01MH121521 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GANDAL, MICHAEL · 2020 to 2024
$3.4M
Population-level and mechanistic dissection of 17q21 structural variant association with psychiatric traitsR01MH123922 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GANDAL, MICHAEL · 2020 to 2024
$3.1M
Tissue Size and Precision Control in Growing Hair FolliclesR01AR079150 · NIAMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Qing Nie, Maksim V Plikus · 2022 to 2026
$2.7M
Development of tools for analyzing cell-cell communication using spatial transcriptomic dataR01GM152494 · NIGMS · UNIVERSITY OF CALIFORNIA-IRVINE · PI Zixuan Cang, Qing Nie · 2024 to 2026
$1.0M
Human cerebral organoids as a model system for neural development and diseaseR00HD096105 · NICHD · UNIVERSITY OF CALIFORNIA-IRVINE · PI WATANABE, MOMOKO · 2020 to 2022
$737k
NIAMS NIH HHS R01 AR079150NICHD NIH HHS R00 HD096105NIGMS NIH HHS R01 GM152494NIMH NIH HHS R01 MH121521NIMH NIH HHS R01 MH123922
6 · The paper itself

Abstract

The human neocortex exhibits characteristic regional patterning (arealization) critical for higher-order cognitive function. Disrupted arealization is strongly implicated in neurodevelopmental disorders (NDDs), but current neocortical organoid models largely fail to recapitulate this patterning, limiting mechanistic understanding. Here, we establish a straightforward method for generating arealized organoids through short-term early exposure to anterior (FGF8) or posterior (BMP4/CHIR-99021) morphogens. These treatments created distinct anterior and posterior signaling centers, supporting long-lasting polarization, which we validated with single-cell RNA sequencing that revealed area-specific molecular signatures matching prenatal human cortex. To demonstrate the utility of this platform, we modeled Fragile X Syndrome (FXS) in organoids with distinct anterior and posterior regional identities. FXS organoids showed highly disrupted SOX4/SOX11 expression gradients along the anterior-posterior axis, consistent with alterations found in autism spectrum disorder (ASD) and demonstrate how regional patterning defects may contribute to NDD pathology. Together, our study provides a robust platform for generating neocortical organoids with anterior-posterior molecular signatures and highlights the importance of modeling NDDs using experimental platforms with neuroanatomic specificity.

Indexed as

autism spectrum disorderbrain organoidsneocortical areal signatures

Identifiers

PMID40950130
PMCPMC12424832

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.